Simultaneous Determination of Rifampicin and Efavirenz in Plasma Marta Boffito,*† John Tija,* Helen E. Reynolds,* Patrick G. Hoggard,* Stefano Bonora,† Giovanni Di Perri,† and David J. Back* *Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom, and †Division of Infectious Disease, University of Torino, Torino, Italy Summary: Complex drug interactions involving antiretroviral agents and drugs for the management of opportunistic infections demand the monitoring of plasma drug concentrations to prevent treatment failure. The high occurrence of tuberculosis in HIV-infected subjects makes the management of HIV treatment complex. Rifampicin, a potent inducer of the cytochrome P 450 metabolic pathway, is a very active antitu- berculosis drug that accelerates the metabolism of protease inhibitors. Regimens con- taining efavirenz, a non-nucleoside reverse transcription inhibitor, could be an alter- native, but efavirenz plasma concentrations may be altered after the coadministration of rifampicin. Efavirenz is also a cytochrome P 450 inducer and may alter rifampicin plasma levels. Due to the increasing need to monitor plasma concentrations in HIV patients with tuberculosis, a high-performance liquid chromatographic (HPLC) method has been developed to measure rifampicin and efavirenz at the same time in a small amount of sample. This HPLC method is highly sensitive and precise, suitable for pharmacokinetic studies or routine clinical monitoring of rifampicin and efavirenz simultaneously in HIV patients with tuberculosis. Key Words: Rifampicin— Efavirenz—High-performance liquid chromatography—Tuberculosis—Antiretrovirals. The potential for drug interactions between antiretro- viral agents and drugs for opportunistic infections is high, leading to altered plasma drug concentrations (1). Marked interindividual variability in plasma concentra- tions coupled with complex drug interactions involving cytochrome P 450 (CYP 450) enzymes and drug trans- porters point to an important role for monitoring of plasma drug concentrations to prevent treatment failure (2). However, therapeutic drug monitoring (TDM) in HIV therapy is still to be fully justified for antiretroviral agents and other drugs needed for the treatment of HIV- positive patients (3). The occurrence of Mycobacterium tuberculosis infec- tion in HIV-positive subjects is higher compared with the general population (4), and clinical management of coin- fected patients is complex. Rifampicin is one of the most active antituberculosis agents available, and it represents the standard of care for the management of M. tubercu- losis infection, in association with other first-line antitu- berculosis drugs. Rifampicin is well known as a potent inducer of CYP 450 enzymes (5) and is contraindicated in combination with protease inhibitors for the manage- ment of tuberculosis in HIV-infected patients (6). There- fore, efavirenz-containing regimens plus rifampicin- containing antituberculosis regimens are recommended in treating HIV-infected patients with active tuberculosis infection (6). Efavirenz is itself a moderate inducer of CYP 450 3A4 activity altering the hepatic metabolism of other drugs (1). The usefulness of drug level moni- toring for efavirenz was demonstrated recently, and treat- ment failure and central nervous system side effects were Received October 3, 2001; accepted February 21, 2002. Address correspondence and reprint requests to Marta Boffito, De- partment of Pharmacology and Therapeutics, University of Liverpool, Ashton Street, Liverpool, L69 3GE, United Kingdom; E-mail: martalbb@hotmail.com Therapeutic Drug Monitoring 24:670–674 © 2002 Lippincott Williams & Wilkins, Inc., Philadelphia 670 DOI: 10.1097/01.FTD.0000022900.08701.89